本文選題：長(zhǎng)時(shí)程增強(qiáng) + NMDA受體��； 參考：《上海交通大學(xué)》2009年碩士論文

【摘要】： NMDA受體廣泛表達(dá)于中樞神經(jīng)系統(tǒng),介導(dǎo)突觸可塑性的形成,調(diào)控神經(jīng)元的基因表達(dá),參與發(fā)育過(guò)程中神經(jīng)網(wǎng)絡(luò)的形成。它是大腦學(xué)習(xí)與記憶功能的關(guān)鍵因子,同時(shí)過(guò)度激活也可導(dǎo)致神經(jīng)元壞死和細(xì)胞凋亡等神經(jīng)損害。NR1是功能性NMDA受體的必需亞基,其C末端由于2個(gè)外顯子的可變剪接而具有分子生物學(xué)多樣性,在很大程度上決定了NMDA受體復(fù)雜多樣的功能。多年來(lái)很多研究都提示NR1亞基C末端對(duì)受體通道功能的調(diào)控,靶向運(yùn)輸及基因表達(dá)等方面起著重要的作用,但其具體的功能及其機(jī)制還未完全闡明。而且這些研究大多是針對(duì)在異源系統(tǒng)或體外培養(yǎng)的神經(jīng)細(xì)胞中表達(dá)的重組受體進(jìn)行的,而重組受體一般會(huì)失去生理狀態(tài)下細(xì)胞內(nèi)環(huán)境中很多信號(hào)分子或結(jié)構(gòu)蛋白的作用,而且這種方法使得我們無(wú)法對(duì)其在突觸可塑性中的作用進(jìn)行研究。因此,有必要構(gòu)建一種C末端特定區(qū)段缺失的轉(zhuǎn)基因動(dòng)物模型,從而在能夠較好模擬在體環(huán)境的條件中進(jìn)行C末端剪接異構(gòu)體的功能研究。本研究中,我們利用合作研究單位構(gòu)建的NR1亞基C末端C1、C2兩個(gè)外顯子被敲除的NR1dC1,C2小鼠,在海馬切片中進(jìn)行了NMDA受體通道性質(zhì)的系統(tǒng)的檢測(cè)。我們的研究結(jié)果顯示NR1dC1,C2小鼠其NMDA受體電流在強(qiáng)刺激、高頻刺激、或者雙刺激的條件下反應(yīng)性減弱,LTP的形成受到抑制。由此我們推測(cè)在海馬CA1神經(jīng)元內(nèi)NR1亞基的C1和/或C2參與CDI的調(diào)控,而C1和C2的缺失導(dǎo)致了CDI程度的增強(qiáng),使得高頻刺激以及雙刺激下NMDA受體介導(dǎo)的Ca2+內(nèi)流受到抑制,使得LTP的形成受到影響。我們的以上研究為進(jìn)一步深入揭示NR1亞基C1和C2外顯子的功能提供了新的線索。
[Abstract]:NMDA receptors are widely expressed in the central nervous system, mediate the formation of synaptic plasticity, regulate the gene expression of neurons, and participate in the formation of neural networks during development.It is a key factor in the learning and memory function of the brain, and excessive activation can also lead to neuronal necrosis and apoptosis. NR1 is an essential subunit of functional NMDA receptor.Its C-terminal has molecular biological diversity due to the variable splicing of two exons, which to a great extent determines the complex and diverse functions of NMDA receptors.Many studies have suggested that the C-terminal of NR1 subunit plays an important role in regulation of receptor channel function, targeted transport and gene expression, but its specific function and mechanism have not been fully elucidated.And most of these studies are directed at recombinant receptors expressed in xenogeneic systems or in cultured nerve cells, which typically lose the role of many signaling molecules or structural proteins in the cellular environment under physiological conditions.And this method makes it impossible to study its role in synaptic plasticity.Therefore, it is necessary to construct a transgenic animal model with missing specific segments of C-terminal, so as to study the function of C-terminal splicing isomers under the condition of better simulation in vivo.In this study, we used co-constructed NR1dC1C2-2 exons of NR1 subunit to detect the properties of NMDA receptor channels in hippocampal slices of NR1dC1C1-C 2 mice.Our results showed that the NMDA receptor current in NR1dC1C 2 mice was inhibited under the condition of strong stimulation, high frequency stimulation, or double stimulation.Therefore, we speculate that C1 and / or C2 of NR1 subunit in hippocampal CA1 neurons are involved in the regulation of CDI, and the deletion of C1 and C2 leads to the enhancement of CDI degree, which inhibits Ca2 influx mediated by NMDA receptor under high frequency stimulation and double stimulation.The formation of LTP is affected.Our study provides a new clue to further reveal the function of exons C1 and C2 of NR1 subunits.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R341

【共引文獻(xiàn)】

相關(guān)期刊論文 前3條

1 羅婭麗;黑明燕;;NMDA受體3A亞基在中樞神經(jīng)系統(tǒng)發(fā)育中的作用[J];海南醫(yī)學(xué)院學(xué)報(bào);2012年02期

2 馮晨;馮磊;;蛋白質(zhì)棕櫚�；瘜�(duì)離子型谷氨酸受體運(yùn)輸?shù)恼{(diào)節(jié)作用[J];中國(guó)生物化學(xué)與分子生物學(xué)報(bào);2010年08期

3 焦聚;馬融;任獻(xiàn)青;;NMDA受體及其與癲癇所致認(rèn)知功能損害的關(guān)系[J];中國(guó)中西醫(yī)結(jié)合兒科學(xué);2014年03期

相關(guān)碩士學(xué)位論文 前1條

1 琚玨剛;突觸外NMDA受體介導(dǎo)的癲癇發(fā)生機(jī)制的電生理學(xué)研究[D];上海交通大學(xué);2010年

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本文編號(hào)：1746917